Psychosocial factors in the development of clinical illness have been extensively documented. It is probable that at least one mode of action of these factors is through modifying host-resistance as an outcome of central nervous system physiology, including hypothalamic neuroendocrine pathways. Since the disposition and metabolism of hypothalamic monoamines, especially dopamine, is reported to be intimately related to several hypothalamic releasing hormones, blood platelet monoamine oxidase (MAO) activity, as a genetically stable marker, is postulated to be a simple screening procedure for hypothalamic dopaminergic physiology. Perhaps psychosocial factors and platelet MAO activity can be ultimately synthesized in a multivariate equation, predicting risk for clinical symptoms of infectious mononucleosis (IM). Such risk for physical illness, when considering preliminary platelet MAO data alone, appears to be antithetically related to risk for certain psychiatric illnesses. Following two successive years of preliminary, prospective studies of IM in college age students, a fully-prospective epidemiologic design has now been generated to include a variety of psychosocial instruments in addition to prospective evaluations of platelet MAO activity. Preliminary evidence to date identifies clinical IM as dependent upon brain and behavior. The existence of a fluorescent method for Epstein-Barr virus (EBV) antibody screening, utilized prospectively, is the principal serological basis upon which clinical IM and inapparent EBV infections are discriminated. Through such means of prospective discrimination, the psychosocial and biochemical risk factors are evaluated and synthesized within the broad interactive fields of modern medicine and psychiatry.